Skin adipocytes help protect against infections Richard Gallo MD Phd professor and chief of dermatology at UC San diego School of medicine and colleagues have uncovered a previously unknown role for dermal fat cells known as adipocytes:
They produce antimicrobial peptides that help fend off invading bacteria and other pathogens. It was thought that once the skin barrier was broken it was entirely the responsibility of circulating (white blood cells like neutrophils
and macrophages to protect us from getting sepsis said Gallo the study's principal investigator. But it takes time to recruit these cells (to the wound site.
We now show that the fat stem cells are responsible for protecting us. That was unexpected totally.
The human body's defense against microbial infection is tiered complex multi and involves numerous cell types culminating in the arrival of neutrophils
and monocytes--specialized cells that literally devour targeted pathogens. But before these circulating white blood cells arrive at the scene the body requires a more immediate response to counter the ability of many microbes to rapidly increase in number.
and leukocytes residing in the area of infection. Staphylococcus aureus is a common bacterium and major cause of skin and soft tissue infections in humans.
The emergence of antibiotic-resistant forms of S. aureus is a significant problem worldwide in clinical medicine.
Prior published work out of the Gallo lab had observed S. aureus in the fat layer of the skin
if the subcutaneous fat played a role in preventing skin infections. Ling Zhang Phd the first author of the paper exposed mice to S. aureus and within hours detected a major increase in both the number and size of fat cells at the site of infection.
More importantly these fat cells produced high levels of an antimicrobial peptide (AMP) called cathelicidin antimicrobial peptide or CAMP.
AMPS are used molecules by the innate immune response to directly kill invasive bacteria viruses fungi and other pathogens.
AMPS are our natural first line defense against infection. They are evolutionarily ancient and used by all living organisms to protect themselves said Gallo.
Too little CAMP and people experience frequent infections. The best example is atopic eczema (a type of recurring itchy skin disorder.
These patients can experience frequent Staph and viral infections. But too much CAMP is also bad.
Evidence suggests excess CAMP can drive autoimmune and other inflammatory diseases like lupus psoriasis and rosacea.
The scientists confirmed their findings by analyzing S. aureus infections in mice unable to either effectively produce adipocytes or
whose fat cells did not express sufficient antimicrobial peptides in general and CAMP in particular. In all cases they found the mice suffered more frequent and severe infections.
Further tests confirmed that human adipocytes also produce cathelicidin suggesting the immune response is similar in both rodents and humans.
or insulin resistance resulting in greater susceptibility to infection but too much cathelicidin may provoke an unhealthy inflammatory response.
For example current drugs designed for use in diabetics might be beneficial to other people who need to boost this aspect of immunity.
Conversely these findings may help researchers understand disease associations with obesity and develop new strategies to optimize care e
#DNA nanoswitches reveal how life's molecules connect Now a new approach developed by researchers at the Wyss Institute for Biologically Inspired Engineering Boston Children's Hospital
Biomolecular interaction analysis a cornerstone of biomedical research is accomplished traditionally using equipment that can cost hundreds of thousands of dollars said Wyss Associate Faculty member Wesley P. Wong Ph d. senior author
Wong who is also Assistant professor at Harvard Medical school in the Departments of Biological Chemistry & Molecular Pharmacology and Pediatrics and Investigator at the Program in Cellular and Molecular Medicine at Boston Children's Hospital calls the new
Professor of Vascular Biology at Boston Children's Hospital and Harvard Medical school and a Professor of Bioengineering at Harvard SEAS.
Biomedical researchers all over the world can start using this new method right away to investigate how biological compounds interact with their targets using commonly-available supplies at very low cost t
Distinguished Professor of Orthopaedic Surgery at the MU School of medicine.""The benefit to patients is that more graft material will be available
This will allow us as surgeons to provide a more natural joint repair option for our patients."
In traditional preservation methods, donated tissues are stored within a medical-grade refrigeration unit in sealed bags filled with a standard preservation solution.
"said study co-author James Cook, director of MU's Comparative Orthopaedic Laboratory and the Missouri Orthopaedic Institute's Division of Research."
schedule surgery and get the graft to the surgeon for implantation.""Stannard, who also serves as chair of MU's Department of Orthopaedic Surgery
and medical director of the Missouri Orthopaedic Institute, said that patients with metal and plastic implants often are forced to give up many of the activities they previously enjoyed
in order to extend the life of their new mechanical joints.""For patients with joint problems caused by degenerative conditions,
metal and plastic implants are still a very good option, "Stannard said.""When the end of a bone that forms a joint is destroyed over time,
However, for patients who experience trauma to a joint that was otherwise healthy before the injury,
However, the method of preserving the grafts themselves has limited the amounts of quality donor tissue available to surgeons.
Cook, who also serves as the William and Kathryn Allen Distinguished Professor in Orthopaedic Surgery at the MU School of medicine,
#Novel compound switches off epilepsy development In temporal lobe epilepsy seizures arise in the hippocampus and other structures of the limbic system located in the temporal lobe when a cascade of molecular and cellular events results in aberrant brain wiring.
The period between a brain injury and the onset of seizures called epileptogenesis is a silent period
because this brain abnormality cannot be detected by current neurological exams or electroencephalography (EEG). Temporal lobe epilepsy (TLE) or limbic epilepsy is a common adult epileptic disorder characterized by spontaneous recurrent seizures that may also spread to other brain regions triggering secondary severe generalized seizures.
Aside from neurosurgery which benefits only a small population of TLE patients there are no other effective treatments or preventive strategies.
Working in a mouse model the research team led by Drs. Nicolas Bazan Boyd Professor and Director of the LSU Health New orleans Neuroscience Center of Excellence and Alberto Musto Assistant professor of Research Neurosurgery and Neuroscience found that brief small electrical microbursts
or microseizures occur before the onset of clinical recurrent seizures. When they systemically administered Neuroprotectin D-1 (NPD1) the researchers discovered that NPD1 regulated these bursts of brain electrical activity that not only reduced the aberrant brain cell signaling leading to severe generalized seizures but also spontaneous recurrent seizures.
Epilepsy is a chronic neurological disorder characterized by recurrent seizures. It's estimated that 66 million people in the world have epilepsy.
In the US 1 in 26 people will develop epilepsy at some time during their lifetime.
The incidence of epilepsy is higher in young children and older adults. Although the cause of epilepsy is unknown there are some types of epilepsy associated with previous brain injury.
Recurrent seizures might cause brain damage. According to the Epilepsy Foundation temporal lobe epilepsy is the most common form of partial or localization related epilepsy.
It accounts for approximately 60%of all patients with epilepsy. The medial form accounts for almost 80%of all temporal lobe seizures.
While medial temporal lobe epilepsy is a very common form of epilepsy it is also frequently resistant to medications.
The overall prognosis for patients with drug-resistant medial temporal lobe epilepsy includes a higher risk for memory and mood difficulties.
This in turn leads to impairments in quality of life and an increased risk for death as observed in patients who have frequent seizures failing to respond to treatment.
These observations will contribute to our ability to predict epileptic events define key modulators of brain circuits especially after a brain injury
and provide potential biomarkers and therapeutic approaches for epileptogenesis says Dr. Musto o
#Researchers use sound to slow down speed up and block light Researchers from the University of Illinois at Urbana-Champaign have demonstrated experimentally for the first time the phenomenon of Brillouin Scattering Induced Transparency (BSIT)
which can be used to slow down speed up and block light in an optical waveguide. The BSIT phenomenon permits light to travel in the forward direction while light traveling in the backward direction is absorbed strongly.
This nonreciprocal behavior is essential for building isolators and circulators that are indispensible tools in an optical designer's toolkit.
#'Healthy'fat tissue could be key to reversing type 2 diabetes Researchers from Melbourne's Walter
and Eliza Hall Institute with colleagues from the RIKEN Institute Japan found they could'reverse'type 2 diabetes in laboratory models by dampening the inflammatory response in fat tissue.
More than 850000 Australians are estimated to have type 2 diabetes which is the most common type of diabetes
and its prevalence is rising. The disease is linked strongly with'lifestyle'factors such as being overweight
or having high blood pressure. Long-term complications of type 2 diabetes include kidney eye and heart disease and there is no cure.
People with type 2 diabetes have reduced sensitivity to insulin a hormone that normally triggers uptake of glucose by cells
and their cells no longer respond to insulin appropriately. This decrease in insulin sensitivity is thought to be a result of long-term low-level inflammation of fat tissue in people who are obese.
Dr Vasanthakumar said Tregs acted as the guardians of the immune system preventing the immune response from getting out of hand-hand
When Treg numbers are reduced inflammatory diseases such as diabetes and rheumatoid arthritis can occur he said. Recent studies have shown that fat tissue has its own unique type of Tregs
and high blood glucose levels a classic hallmark of type 2 diabetes. The research team discovered a key hormone called IL-33 (interleukin-33) was able to selectively boost Treg populations in fat tissue effectively halting the development of type 2 diabetes
or even reversing the disease in preclinical models. Treating fat tissues with IL-33 restored normal Treg cell levels
which reduced inflammation and decreased blood glucose levels Dr Vasanthakumar said. Treatments that mimic IL-33 could have the potential to reduce obesity-related inflammation and type 2 diabetes.
Dr Kallies said the research underscored the importance of'healthy'fat tissue in maintaining a healthy body.
and our research highlights the important role it plays in preventing disease e
#From bacterium to biofactory Research team including Dr. Stefan Schiller, his assistants Dr. Matthias Huber and Dr. Andreas Schreiber,
The approach opens up new possibilities for the study of biomedical processes as well as for applications in biotechnology, chemistry, and pharmacy."
and medicine,"says Schiller. With the help of chemical reactions that were previously impossible in the cell,
or the allergy-inducing ragweed (Ambrosia artemisiifolia) will end up on the"Union List","as the cost of eliminating them would be too high."
#Key discovery to preventing blindness stroke devastation Studying the eye and the brain might hold the key to creating therapeutic solutions for blindness stroke
and other seemingly unrelated conditions associated with the central nervous system notes Dr. Bazan. The eye is a window to the brain.
or die when threatened with disease onset. The gene mechanism that we discovered is the interplay of two genes turned on by the messenger Neuroprotectin D1.
Age-related macular degeneration (AMD) is a devastating disease that targets the retina of the elderly
The causal mechanisms of this disease remain elusive. The retinal pigment epithelium (RPE is a single layer of cells that accomplishes multiple functions such as providing survival molecules that prevent photoreceptors from dying.
They showed that NDP1 bioactivity governs key gene interactions decisive in cell survival when threatened by disease or injury.
but it also promotes remarkable neurological recovery from the most frequent form of stroke in humans s
#Using 3-D printing clinicians repair tracheal damage Mr. Goldstein a Phd candidate at the Hofstra North Shore-LIJ School of medicine has been working with a team of surgeons at the North Shore
Tracheal damage can be caused by tumor endotracheal intubation blunt trauma and other injuries. Narrowing and weakness of the trachea can occur
Lee Smith MD chief of pediatric otolaryngology at Cohen Children's Medical center and David Zeltsman MD chief of thoracic surgery at Long island Jewish Medical center both part of
and Daniel A. Grande Phd director of the Orthopedic Research Laboratory at the Feinstein Institute and asked
With 3d printing we were able to construct 3d printed scaffolding that the surgeons could immediately examine
The advantage of PLA is that it's used in all kinds of surgical implant devices says Dr. Smith.
and fills in gaps in the PLA scaffolding then cures into a gel on the heated build plate of the Makerbot Replicator 2x.
and Dr. Zeltsman at The Society of Thoracic Surgeons illustrate how the 3d printed windpipe or trachea segments held up for four weeks in an incubator.
Medical research can take years to move from bench to bedside as can US Food and Drug Administration (FDA) approval.
However if there is no approved treatment for an ailment the FDA has a compassionate therapy exception that allows the patient to agree to try an experimental approach.
and tools to improve the lab. He is the presenting author on a paper being presented to thousands of surgeons
which will be available commercially later this year so the Feinstein Institute can start investigating how to engineer other kinds of tissue like bone or 3d print custom-made shields for cancer and radiation treatment.
#Modular disability aids for world's poorest Inspiration hit Cara O'sullivan 21 from Battle East Sussex after a year's placement with the Medical Engineering Resource Unit (MERU
The changes that MERU products can make to the lives of children with disabilities inspired
which offers support to young people with disabilities and their families living in poverty in Peru and Tanzania.
#Probiotic helps treat diabetes in rats could lead to human remedy In the study published Jan 27 in the journal Diabetes the researchers engineered a strain of lactobacillus a human probiotic common in the gut to secrete a Glucagen-like peptide
(GPL-1). They then administered it orally to diabetic rats for 90 days and found the rats receiving the engineered probiotic had up to 30 percent lower high blood glucose a hallmark of diabetes.
The study was a proof of principle and future work will test higher doses to see
The researchers found that upper intestinal epithelial cells in diabetic rats were converted into cells that acted very much like pancreatic beta cells
Also though it replaces the insulin capacity in diabetic rats the researchers found no change in blood glucose levels
. which is working to get the therapy into production for human use. Human patients would likely take a pill each morning to help control their diabetes March said d
#Unique aortic aneurysm repair shows promise A novel, minimally invasive approach appears safe for treating life-threatening aneurysms that occur in the deepest part of the aorta,
making it easier for surgeons to repair the aorta without opening the chest and easier for patients to recover.
The approach was described today at the 51st Annual Meeting of The Society of Thoracic Surgeons.
The aorta is the major vessel that carries blood from the heart to the body and has branches that reach all organs in the body.
An aneurysm occurs when the wall of the vessel weakens, and if an aneurysm in the aorta bursts, it can lead to death in a matter of minutes."
"Currently, thoracic aortic aneurysms that reach into the aortic arch are very difficult to treat with minimally invasive endovascular methods
The surgeons performed the entire procedure using only a small incision in the groin (inner thigh.
"said co-author Joseph E. Bavaria, MD, from the Hospital of the University of Pennsylvania in Philadelphia."
While our study only addressed aneurysms, the results have implications for cardiothoracic surgeons who perform procedures to repair tears in the ascending aorta (type A dissection),
whether this treatment will be safe and effective in aneurysms that extend a little closer to the heart within the aorta,
#New breast cancer risk prediction model more accurate than current model A new breast cancer risk prediction model combining histologic features of biopsied breast tissue from women with benign breast disease
Results of a Mayo Clinic study comparing the new model to the current standard, the Breast cancer Risk Assessment Tool (BCRAT), are published in the Journal of Clinical Oncology."
"Physicians routinely perform biopsies to evaluate concerning findings in the breast, either felt on exam
or seen on mammogram, for the presence of a breast cancer,"says Amy Degnim, M d.,a surgeon at Mayo Clinic and a senior author of the study."
"However, about three-quarters of these biopsies prove to be benign and are referred to as benign breast disease (BBD)."
"Annually, more than a million American women have a biopsy with a benign finding and are left wondering
if they will later develop breast cancer. Dr. Degnim and her colleagues hypothesized that certain breast tissue findings,
while benign, could help predict which women were increased at risk of developing breast cancer later.""Our new model more accurately classifies a woman's breast cancer risk after a benign biopsy than the BCRAT,
"Dr. Degnim says. Developed by the National Cancer Institute and the National Surgical Adjuvant Breast and Bowel Project, BCRAT is currently the most commonly used model for predicting breast cancer risk in women with BBD.
To test the new model, Dr. Degnim and her colleagues studied a cohort of approximately 10,000 women who had benign breast biopsies at Mayo Clinic
and who received long-term follow-up for a later breast cancer occurrence. Using this cohort researchers determined the age-specific incidence of breast cancer and death,
and 734 matched controls sampled from the Mayo Clinic BBD cohort. They validated the model using an independent set of women from the Mayo BBD cohort (378 patients with a later breast cancer
The BCRAT significantly underpredicted breast cancer risk after benign biopsy (P. 004), whereas predictions derived from the new model were calibrated appropriately to observed cancers (P. 247)."
"Since women with benign breast disease are at higher risk for breast cancer, optimal early detection is extremely important,
"Dr. Degnim says.""Ideally, women at increased risk for breast cancer should be identified so that we can offer appropriate surveillance and prevention strategies.
and neuroscientists to use to address questions ranging from fundamental mechanisms in cell biology to the underlying causes of mental illness to the discovery of novel therapeutics.
Ultimately it will help researchers achieve breakthroughs in a wide variety of areas in the life sciences such as neuroscience diabetes and cancer.
#Treating Cerebral Malaria: New Molecular Target Identified A drug already approved for treating other diseases may be useful as a treatment for cerebral malaria, according to researchers at Harvard T. H. Chan School of Public health.
They discovered a novel link between food intake during the early stages of infection and the outcome of the disease, identifying two molecular pathways that could serve as new targets for treatment."
"We have known for a long time that nutrition can affect the course of infectious disease, but we were surprised at how rapidly a mild reduction in food intake could improve outcome in a mouse malaria model,
"said senior author James Mitchell, associate professor of genetics and complex diseases.""However, the real importance of this work is the identification of unexpected molecular pathways underlying cerebral malaria that we can now target with existing drugs."
"The study appears online January 30, 2015 in Nature Communications. Cerebral malaria--a severe form of the disease--is the most serious consequence of infection by the parasite Plasmodium falciparum,
resulting in seizures, coma, and death. Currently there is a lack of safe treatment options for cerebral malaria, particularly for use in children,
who represent the majority of cases. Even patients who receive early treatment with standard antimalarial chemotherapeutic agents run a high risk of dying,
despite clearance of the parasite. Moreover, around 25%of survivors develop neurological complications and cognitive impairment.
Lead authors Pedro Mejia and J. Humberto Treviño-Villarreal both researchers at Harvard T. H. Chan School of Public health, found that leptin--a hormone secreted from fat tissue with roles in suppressing appetite,
but also in activating adaptive immune and inflammatory responses--is increased upon infection in a mouse model of cerebral malaria,
and turns out to be a major bad actor in promoting neurological symptoms and death. Remarkably, Mejia, Treviño-Villarreal and colleagues showed that reducing leptin using a variety of means,
either genetically, pharmacologically, or nutritionally by reducing food intake during the first two days of infection, protected against cerebral malaria.
The researchers also found that leptin acted primarily on cytotoxic T cells by turning on the well-studied mtor protein
for which pharmacologic inhibitors are readily available. In their animal model, treating mice with the mtor inhibitor rapamycin protected them against the neurological complications of cerebral malaria.
Protection was due in part to a preservation of the blood brain barrier, which prevented the entry of blood cells carrying the parasites into the brain.
As rapamycin is approved already FDA for use in humans, trials in humans for cerebral malaria treatment with this drug may be possible, according to the researchers e
#Hydrogen production in extreme bacterium Researcher at Missouri University of Science and Technology has discovered a bacterium that can produce hydrogen,
#Device for guided surgery of deviations in long bones patented CEU-UCH Cardenal Herrera University patented a device that can be applied in surgeries to correct deviations in long bones.
and enables a surgeon to set the cutting angle that best suits the bone, and, also, to set the location
and could have applications in orthopedic surgery on humans. Angular deviations in the bones of body extremities cause physical overload that, in the case of dogs and other animals that develop those bones in the course of only a few months,
can only be corrected through a surgical intervention. After mandatory medical criteria have been met, the device our university patented could have applications in adult humans,
such as to treat fractures and other pathologies that cause this kind of deviations in the bones of adult people.
so that a specific deviated bone can be realigned through surgery. To determine the suitable formula, the bone that is to be operated on is reconstructed first in 3d on the basis of an CT SCAN,
the personalized device that the surgeon uses to determine the optimal points and cutting angles is designed and produced.
has so far been used in seven orthopaedic surgical interventions on dogs in which Iván Serra,
These surgeries, which in three dimensions corrected deviations in bones, yielded some very satisfying results.
International dissemination of the investigation This new device for surgery of angular deviations in long bones was presented to experts in engineering and veterinary medicine at two international congresses.
The results of the first surgical interventions on dogs were presented in the presence of UCV professor of Veterinary medicine Iván Serra, at the 17th European Society of Veterinary Orthopaedics and Traumatology Congress,
#How cancer turns good cells to the dark side A new computational study by researchers at the Rice-based Center for Theoretical Biological Physics shows how cancer cells take advantage of the system by
and Jos Onuchic the researchers decode how cancer uses a cell-cell interaction mechanism known as notch signaling to promote metastasis. This mechanism plays a crucial role in embryonic development
and wound healing and is activated when a delta or jagged ligand of one cell interacts with the notch receptor on an adjacent one.
which the researchers mapped the flow of information through genetic circuits involved in cancer metastasis. At the heart of our new understanding is that the primary agents of metastasis are clusters of hybrid epithelial (nonmobile)
These and not the fully mesenchymal cells are the'bad actors'of cancer progression that pose the highest risk.
The multifaceted mechanism by which notch-delta-jagged signaling promotes cancer progression has been a mystery until now Ben-Jacob said
but recent experimental studies have revealed the jagged ligand plays a critical role in tumor progression.
Cancer takes advantage of jagged proteins'influence to form what are essentially migrating units of hybrid cancer stem cells Ben-Jacob said.
Notch-jagged signaling also helps cells develop resistance to chemotherapy and radiotherapy and facilitates metastasis formation by promoting communications between cancer
and stromal (connective tissue) cells at the new locations he said. Recent findings showed stromal cells in the tumor environment secrete jagged ligands.
The Rice researchers found cancer cells hijack nearby stromal cells and prompt them to boost their production of the ligand reinforcing the cancer's chances of survival.
The researchers suggested cells'internal expression of jagged may also increase the production and maintenance of therapy-resistant cancer stem cells.
Because they have a high likelihood to acquire stem-like properties when arriving at distant organs they utilize this cellular plasticity to differentiate
#New breast exam nearly quadruples detection of invasive breast cancers in women with dense breast tissue Molecular Breast Imaging (MBI) is a supplemental imaging technology designed to find tumors that would otherwise be obscured by surrounding dense breast
Tumors and dense breast tissue can both appear white on a mammogram making tumors indistinguishable from background tissue in women with dense breasts.
About half of all screening-aged women have dense breast tissue according to Deborah Rhodes M d. a Mayo Clinic Breast Clinic physician
MBI uses small semiconductor-based gamma cameras to image the breast following injection of a radiotracer that tumors absorb avidly.
Unlike conventional breast imaging techniques such as mammography and ultrasound MBI exploits the different behavior of tumors relative to background tissue producing a functional image of the breast that can detect tumors
The study conducted at Mayo Clinic included 1585 women with heterogeneously or extremely dense breasts who underwent an MBI exam at the time of their screening mammogram.
The finding that MBI substantially increases detection rates of invasive cancers in dense breasts without an unacceptably high increase in false positive findings has important implications for breast cancer screening decisions particularly as 20 states now require mammography facilities
and encourage discussion of supplemental screening options says Dr. Rhodes. These findings suggest that MBI has a more favorable balance of additional invasive cancers detected
versus additional biopsies incurred relative to other supplemental screening options. Recent studies have reported supplemental cancer detection rates of 1. 9 per 1000 women screened with automated whole breast ultrasound
and 1. 2 to 2. 8 per 1000 women screened with digital breast tomosynthesis so our finding of an additional 8. 8 cancers per 1000 women makes MBI a very compelling option for women who elect supplemental screening says Dr. Rhodes. Michael O'connor Ph d. a Mayo Clinic scientist
and inventor of the MBI technology calls this latest study a major milestone for both safety
because it incorporates many of the advances in MBI pioneered here at Mayo Clinic and shows that studies can be performed safely with low radiation exposure to the patient says Dr. O'connor. This means MBI is safe and effective as a supplemental screening tool.
what MBI can offer women with dense breasts says Amy Conners M d. chair of Mayo Clinic's Breast Imaging Division
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